ArticlePloS one2015
Neuregulin 1 expression and electrophysiological abnormalities in the Neuregulin 1 transmembrane domain heterozygous mutant mouse.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 22 citations in OpenAlex.
- Impaired extinction of operant cocaine in a genetic mouse model of schizophrenia risk.Psychopharmacology · 2023Article
- Differential Effects of Chronic Methamphetamine Treatment on High-Frequency Oscillations and Responses to Acute Methamphetamine and NMDA Receptor Blockade in Conscious Mice.Brain sciences · 2022Article
- Differential Effect of Dopamine D4 Receptor Activation on Low-Frequency Oscillations in the Prefrontal Cortex and Hippocampus May Bias the Bidirectional Prefrontal-Hippocampal Coupling.International journal of molecular sciences · 2022Article
- The effects of preventative cannabidiol in a maleFrontiers in cellular neuroscience · 2022Article
- Integrative Analysis of Neuregulin Family Members-Related Tumor Microenvironment for Predicting the Prognosis in Gliomas.Frontiers in immunology · 2021Article
- High-Frequency Neuronal Oscillatory Abnormalities in the Phospholipase C-β1 Knockout Mouse Model of Schizophrenia.The international journal of neuropsychopharmacology · 2019Article
- Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies.British journal of pharmacology · 2017Review
- Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.Schizophrenia bulletin · 2017Article
- Sensory processing in autism spectrum disorders and Fragile X syndrome-From the clinic to animal models.Neuroscience and biobehavioral reviews · 2017Review
- Neuregulin-1 attenuates cognitive function impairments in a transgenic mouse model of Alzheimer's disease.Cell death & disease · 2016Article
- Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus.Journal of neurodevelopmental disorders · 2016Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Neuregulin 1 transmembrane domain heterozygous mutant (Nrg1 TM HET) mouse is used to investigate the role of Nrg1 in brain function and schizophrenia-like behavioural phenotypes. However, the molecular alterations in brain Nrg1 expression that underpin the behavioural observations have been assumed, but not directly determined. Here we comprehensively characterise mRNA Nrg1 transcripts throughout development of the Nrg1 TM HET mouse. In addition, we investigate the regulation of high-frequency (gamma) electrophysiological oscillations in this mutant mouse to associate molecular changes in Nrg1 with a schizophrenia-relevant neurophysiological profile.
methodsUsing exonic probes spanning the cysteine-rich, epidermal growth factor (EGF)-like, transmembrane and intracellular domain encoding regions of Nrg1, mRNA levels were measured using qPCR in hippocampus and frontal cortex from male and female Nrg1 TM HET and wild type-like (WT) mice throughout development. We also performed electrophysiological recordings in adult mice and analysed gamma oscillatory at baseline, in responses to auditory stimuli and to ketamine.
resultsIn both hippocampus and cortex, Nrg1 TM HET mice show significantly reduced expression of the exon encoding the transmembrane domain of Nrg1 compared with WT, but unaltered mRNA expression encoding the extracellular bioactive EGF-like and the cysteine-rich (type III) domains, and development-specific and region-specific reductions in the mRNA encoding the intracellular domain. Hippocampal Nrg1 protein expression was not altered, but NMDA receptor NR2B subunit phosphorylation was lower in Nrg1 TM HET mice. We identified elevated ongoing and reduced sensory-evoked gamma power in Nrg1 TM HET mice.
interpretationWe found no evidence to support the claim that the Nrg1 TM HET mouse represents a simple haploinsufficient model. Further research is required to explore the possibility that mutation results in a gain of Nrg1 function.
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